Breathing disorder detection and therapy device for providing intrinsic breathing

ABSTRACT

A device and method are provided for managing the treatment of a patient with respiratory disorders or symptoms. Respiratory parameters are sensed and recorded and communicated to an external device to provide information to a patient and/or provider for further treatment or diagnosis. Also respiratory disorders such as apnea or hypoventilation may be treated by electrically stimulating the diaphragm muscle or phrenic nerve in response to a sensed respiratory parameter or characteristic.

FIELD OF THE INVENTION

The invention relates to a device and method for detection, diagnosisand treatment of breathing insufficiencies or irregularities and to themanagement of pulmonary rhythm. Such irregularities may include, forexample, hyperventilation, hypoventilation and apnea. The invention alsorelates to stimulating respiration in response to detectinghypoventilation or apnea.

BACKGROUND OF THE INVENTION

Breathing insufficiencies and irregularities may occur in conjunctionwith or as a result of a variety health related disorders and mayfurther cause or exacerbate health disorders. Such breathinginsufficiencies and irregularities may include, for example,hyperventilation, hypoventilation, apnea, and other related breathingdisorders. Hyperventilation, which results in hyperoxia, is a conditionin which the respiratory rate is pathologically high or is above adesired rate. Hyperventilation may occur due to pulmonary edema orexcess fluid built up in the lungs and may ultimately result in apneaepisodes. Hypoventilation is a condition in which the respiratory rateis pathologically low or below a desired rate. Apnea (absence ofbreathing) is a breathing disorder most typically occurring during sleepthat can result from a variety of conditions. Sleep apnea typicallyresults in some sort of arousal or wakefulness following cessation ofbreathing.

Sleep disordered breathing disorders include two types of sleep apnea:obstructive sleep apnea (partial apnea or obstructive apnea) and centralsleep apnea. Obstructive sleep apneas result from narrowing of thepharynx with out-of-phase breathing in an effort to create airflow,whereas central sleep apnea arises from reductions in centralrespiratory drive. During obstructive sleep apnea, respiratory effortincreases. In central sleep apnea, respiratory movements are absent orattenuated but in phase.

Disordered breathing may contribute to a number of adversecardiovascular outcomes such as hypertension, stroke, congestive heartfailure, and myocardial infarction. Sleep-related breathing disorders,especially central sleep apnea, have been found to have a relativelyhigh prevalence in patients with heart failure and may have a causativeor influencing effect on heart failure. In about 50% of patients withstable congestive heart failure, there is an associated sleep disorderedbreathing, predominantly central sleep apnea with a minority havingobstructive sleep apnea. Furthermore, sleep related breathing disordersare believed to be physiologically linked with heart failure. Centralsleep apnea is a known risk factor for diminished life expectancy inheart failure. It is also believed that in view of this link, treatmentaimed at relieving sleep related breathing disorders may improvecardiovascular outcomes in patients with heart failure.

Pulmonary edema, a condition in which there is excess fluid in the lungsand often found in heart failure patients, is believed in somecircumstances to lead to hyperventilation and hyperoxia or apnea. Mostheart failure patients with central sleep apnea, when lying flat, tendto have central fluid accumulation and pulmonary congestion, whichstimulates vagal irritant receptors in the lungs to cause reflexhyperventilation. Central Sleep Apneas usually are initiated byreduction in PCO₂ resulting from the increase in ventilation. When PCO₂falls below the threshold level required to stimulate breathing, thecentral drive to respiratory muscles and airflow cease or diminishsignificantly and apnea (or attenuated breathing) ensues until the PCO₂rises again above the threshold required to stimulate ventilation. Oftenspontaneous arousal occurs with apnea.

Currently a number of methods are used to treat sleep apnea. Forexample, supplemental oxygen such as, e.g., with a nasal ventilator, hasbeen used to relieve symptoms of sleep apnea. Non-invasive airwaypressure including continuous positive airway pressure (CPAP), bivalveand adaptive pressure support servo-ventilation have been used to treatcentral sleep apnea and obstructive sleep apnea with varying results.Another method to treat central sleep apnea is using aggressive diuresisto lower cardiac filling and beta-blocker and angiotensin-convertingenzymes. However, this treatment does not lead to an optimum therapysince excessive use of diuretics leads to renal complications andpatient discomfort.

A method and apparatus for treatment of obstructive sleep apnea has beenproposed where an implantable pulse generator stimulates a nerve in theupper airway tract of a patient to elicit a contraction by an innervatedmuscle through the provision of electrical stimuli. The stimulator isintended to treat the obstructed airway passage to permit breathing. Thepulse generator is attached to electrodes placed on the patient'sdiaphragm for sensing the respiratory effort of a patient whereupon thestimulation is adjusted. The method and apparatus do not provide asatisfactory treatment or central sleep apnea.

Phrenic nerve stimulation has been used to stimulate the diaphragmthroughout an overnight period to treat sleep apnea. The device used wasturned on at night to stimulate the nerve continuously and then turnedoff during the day. However, this device was not adapted for situationswhere patients would breath spontaneously.

Accordingly it would be desirable to provide a method and apparatus fortreating breathing disorders such as apnea, and hypoventilation, andespecially central sleep apnea. Furthermore it would be desirable toprovide treatments for breathing related disorders related pulmonaryedema and conditions in heart failure patients.

SUMMARY OF THE INVENTION

The present invention provides a method and apparatus for treatingbreathing disorders by sensing the respiratory parameters of thediaphragm and stimulating an associated body organ or tissue to controlmovement of the diaphragm and thus manage respiration. In a variationthe method and apparatus provide stimulation to the diaphragm to elicitdiaphragm movement to cause respiration when respiration ceases or fallsbelow a threshold level.

One embodiment is a device comprising: a sensor for sensing informationcorresponding to respiratory effort of the diaphragm and a processor forprocessing the sensed information and delivering electrical stimulatingpulses to the associated body organ or tissue based on sensedinformation. The processor may further determine stimulation parametersbased at least in part on sensed information. Also, the processor maydetermine when to cease stimulation by determining when the body resumesnormal respiratory function.

The respiratory effort may be sensed, for example, by sensing thephrenic nerve activity and/or the EMG of the diaphragm, or by detectingmovement of the diaphragm or chest. Respiration by, the diaphragm may bestimulated by electrically stimulating the phrenic nerve and/or bystimulating the diaphragm muscle.

A number of different parameters may be programmed into the processor todetermine if certain breathing disorders are present, and when and howto stimulate respiration, and when to stop or modify stimulation.

Phrenic nerve or EMG activity sensed may include, for example,amplitude, frequency, and waveform to determine central respiratoryefforts, the absence, a decrease in amplitude, abnormalities infrequency and/or amplitude, or waveform morphology of which may indicatethe onset of apnea, hyperventilation, or hypoventilation. The nerveactivity may be compared to predetermined activity levels or patienthistorical activity. Similarly, diaphragm EMG amplitude, frequency,waveform morphology and history may be used to determine apnea,hyperventilation and hypoventilation. For example, the nerve activity atthe onset of sleep or after a given time in a reclining position, may beused as a baseline or comparison.

An awake sinus zone may be defined as a respiratory rate or range ofraces programmed into the device for a specific patient when awake,where the respiratory race is considered normal and intrinsic. Apreprogrammed EMG amplitude or range may define a normal rance in thisstate. A sleep sinus may be defined as a respiratory rate or range ofrates programmed into the device for a specific patient when asleepwhere the respiratory rate is considered normal and intrinsic. Apreprogrammed EMG amplitude or range may define a normal range in thisstate. The device may be programmed to match the EMG rate and amplitudeto a normal rate and amplitude by auto adjusting the pace output.

Hypoventilation may be detected where the respiratory rate or frequencyfalls below a programmed rate. Hyperventilation may be detected when therespiratory rate or frequency is above a programmed rate. Complete apneaor central apnea is defined as a condition where there is no effectiveEMG signal or phrenic nerve signal, i.e. where there is no effective orsignificant physiological response. Frequently, a hyperventilationepisode is followed by loss of diaphragm EMG or phrenic nerve activity.The device may be programmed to first detect the hyperventilation andwait for a preprogrammed time to be considered apnea. For example thetime may be set to 10-20 seconds of lost EMG after a hyperventilationepisode to detect complete apnea. Partial apnea or obstructive sleepapnea is defined to be present when the EMG or phrenic nerve activity isattenuated and may be detected when the amplitude drops below aprogrammed amount. For example such amount may be based on the EMG orphrenic nerve amplitude dropping a percentage, e.g. 50% of the SleepSinus EMG amplitude. Also the phase of the respiratory cycles in partialapnea may be determined or compared to an in phase cycle. An cut ofphase or arrhythmic cycle may also be used to detect partial apnea.

In addition, position sensors may be used to determine degree of patientreclining or standing, e.g., in increments of degrees. Information fromthe position sensor mart be used as a tool to match respiratoryactivities and patterns to the position of the patient. Accelerometerinformation may be used to determine information regarding patient'sphysical activity, e.g., to match/compare to the respiratory patternsand activities and collect data on related patient activities,respiratory activities, and create or adjust a treatment plan basedthereon, (e.g., modification of diuretics or ACE inhibitors).Accelerometer sensors may also be used to determine informationregarding movement pattern of the diaphragm muscles, intercostalmuscles, and rib movement and thus determine overall respiratoryactivity and patterns.

According to an embodiment, a stimulator includes an implantablecontroller coupled through leads to electrodes to be implanted on thediaphragm in the vicinity of the phrenic nerve branches. The electrodesmay sense either nerve activity or EMG signals of the diaphragm. Thestimulator may further include a pulse generator configured to deliverstimulating pulses, either to the same electrodes used for sensing or toadditional stimulation electrodes. The stimulation electrodes may alsobe placed adjacent the phrenic nerve at some point along its length toprovide stimulation pulse to the nerves, which in turn enervate thediaphragm muscle causing contractions and resulting respiration.Alternatively the electrodes may be placed on the phrenic nerve for bothsensing and stimulation.

Stimulation of respiration may be initiated when “no” or “attenuated”respiratory activity has been present or detected for a time period(when apnea is detected). The time period may be pre-programmed for aspecific patient by the physician, as otherwise preset, or as determineda program in the treatment device. The device may be programmable forother breathing disorders, allowing slow or fast inspiration and visaversa allowing slow or fast expiration. For example, based on programmedparameters of the activity sensor, for patients suffering fromhypoventilation, the inspiration rate may be increased or decreasedbased on the level of activity.

Pacing starts at given intervals. In one embodiment the interval time isinitially about 10 seconds. The interval is slowly increased from 11seconds to about 15 seconds. If the patient does not breath on theirown, the pacing begins again at 10-second intervals and this isrepeated. If the patient begins breathing on their own, typically wherethe PO₂ and PCO₂ levels are normalized and the brain resumes sendingnerve stimulation. The system then returns to the mode where it issensing respiratory effort.

An additional feature of the invention may include a patientself-management module. The module can be an external device configuredto telemetrically communicate with the implanted device. The module isconfigured to communicate information with the patient based on what isreceived from the implantable device. The information may also becommunicated with a provider who can upload information regarding thestatus of the patient including urgent interventions. The device mayinclude, paging, e-mail, fax or other communication capabilities thatcan send information to a clinician. The device can be worn or carriedwith the patient while the patient is away from home. The device may beused to prompt the patient to comply with life-style and medicationbased on programmed parameters by the provider. The device may requirethe patient to interact with the device confirming compliance. Theprovider may receive information on patient compliance.

The information that may be downloaded for sleep apnea treatment mayinclude, e.g., detection rate, detection amplitude, pacing therapyamplitude, pacing pulse width, pacing frequency or other stimulationwaveform morphology. This information may be used to calibrate devicedetection and therapy parameters.

The information that may be downloaded for pulmonary edema management(e.g., of hyperventilation rate and frequency of occurrence) may includethe detections rate, detection amplitude, ventilation waveformmorphology including slopes and surface of inspiration waveform, slopesand surface area of exhalation waveform, recorded respiratory waveforminformation in conjunction with activity and position sensorsinformation. A provider may use the information in developing an optimumtreatment plan for the patient including drug titrations for diureticmanagement as well as if patient is in need of urgent attention leadingto hospitalization, which is a frequent occurrence with heart failurepatients dealing with pulmonary edema. The patient complianceinformation may also be used for understanding the drug regimeneffectiveness if patient complies or educate the patient when there islack of compliance with the therapy plan.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a sleet breathing disorder treatment device inaccordance with the invention placed on the diaphragm.

FIG. 5 illustrates an electrode assembly in accordance with theinvention implanted on the abdominal side of the diaphragm.

FIG. 3 illustrates a sleep breathing disorder treatment device inaccordance with the invention placed on the phrenic nerves.

FIG. 4 illustrates a sleep breathing disorder treatment device inaccordance with the invention placed on the diaphragm and phrenicnerves.

FIG. 5 illustrates a sleep breathing disorder treatment device inaccordance with the invention placed on the phrenic nerves.

FIG. 6 illustrates a processor unit of a sleep breathing disordertreatment device in accordance with the invention.

FIG. 7A is a schematic of a signal processor of the processor unit inaccordance with the invention.

FIG. 7B is an example of a waveform of an integrated signal processed bythe signal processor of FIG. 7A.

FIG. 8 is a schematic of an external device of a stimulator inaccordance with the invention.

FIGS. 9A-9D are flow diagrams of the operation of a stimulator inaccordance with the invention.

FIG. 9B is a flow diagram of sleep apnea treatment with a stimulator inaccordance with the invention.

FIG. 9C is a flow diagram of hypoventilation treatment with a stimulatorin accordance with the invention.

FIG. 9D is a flow diagram of hyperventilation treatment with astimulator in accordance with the invention.

FIG. 10A-10B are an illustration of a variety of stimulation bursts withdifferent parameters (FIG. 10B) corresponding to different resulting EMGsignals (FIG. 10A).

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates a stimulator 20 comprising electrode assemblies 21,22, each comprising a plurality of electrodes 21 a-d and 22 a-drespectively. The electrode assemblies 21, 22 are implanted in thediaphragm muscle so that one or more of electrodes 21 a-d and toelectrodes 22 a-d are approximately adjacent to one or more junctions ofthe phrenic nerves 15, 16, respectively, with the diaphragm 18 muscle.The electrode assemblies 21, 22 sense and pace at the diaphragm muscle.They are implanted laparoscopically through the abdomen and into themuscle of the diaphragm 18 with needles or other similar devices. Theelectrode assemblies 21, 22 may be anchored with sutures, staples, orother anchoring mechanisms typically used with implantable EMGelectrodes. The leads 23, 24 coupling the electrode assemblies 21, 22 tothe control unit 100 are then routed subcutaneously to the side of theabdomen where a subcutaneous pocket is created for the control unit 100.The electrode assemblies 21, 22 are each flexible members (such asneurostimulation leads) with electrodes 21 a-d, assembled about 5-20 mmapart from one another and electrodes 22 a-d assembled about 5-20 mmapart from one another. The electrode assemblies 21, 22 are coupled vialeads 23, 24 to control unit 100. The control unit 100 is configured toreceive and process signals corresponding to sensed nerve activity,and/or EMG of the diaphragm 18, to determine the respiratory parametersof the diaphragm 18 as described in more detail herein with reference toFIGS. 6, 7A-7B and 9A-9D.

The electrodes assemblies 21, 22 are coupled via leads 23, 24 toinput/output terminals 101, 102 of a control unit 100. The leads 23, 24comprise a plurality of electrical connectors and corresponding leadwires, each coupled individually to one of the electrodes 21 a-d, 22a-d. The control unit 100 is implanted subcutaneously within thepatient, for example in the chest region on top of the pectoral muscle.The control unit 100 is configured to receive sensed nerve electricalactivity from the electrode assemblies 21, 22, corresponding torespiratory effort of a patient. The control unit 100 includes aprocessor 105 (FIG. 6) that delivers stimulation to the nerves 15,16 ordiaphragm 18 in response to a sensed degree or absence of diaphragmrespiratory effort as determined and processed by the processor 105 andcontrol unit 100 as described in more detail herein with reference toFIGS. 6, 7A-7B and 9A-9D.

The stimulator 20 also comprises movement detectors 25, 26, in thisexample, strain gauges included with the electrode assemblies 21, 22respectively and electrically connected through leads 23, 24 to thecontrol unit 100. The movement detectors 25, 26 detect movement of thediaphragm 18 and thus the respiratory effort exerted by the diaphragm18. The movement detectors 25, 26 sense mechanical movement and delivera corresponding electrical signal to the control unit 100 where theinformation is processed by the processor 105. The movement may be usedto qualify the electrical phrenic nerve or EMG signal sensed by thedevice to confirm inspiration or exhalation is occurring, e.g., bymatching mechanical and electrical activities of the diaphragm.

Electrodes may be selected from the plurality of electrodes 21 a-d and22 a-d (or electrodes 41 a-h, 42 a-h, 61 a-d, 62 a-d, 71 a-d, 72 a-d inthe other examples described herein) once implanted, to form bipolar ormultipolar electrode pairs or groups that optimize the stimulationresponse. Such desired response may include tidal volume, breathing rateand the slopes of the inhalation and exhalation curves. For example, atimed series of pulses may be used to create a desired respiratoryinhalation and/or exhalation period. Testing the response may be done byselecting a bipolar electrode pair from two of the multiple electrodesin an assembly or any other combination of electrodes to form at leastone closed loop system, by selecting sequence of firing of electrodegroups and by selecting stimulation parameters. The electrodes may beselected by an algorithm programmed into the processor that determinesthe best location and sequence for stimulation and/or sensing nerveard/or EMG signals, e.g., by testing the response of the electrodes bysensing respiratory effort in response to stimulation pulses.Alternatively, the selection process may occur using an externalprogrammer that telemetrically communicates with the processor andinstructs the processor to cause stimulation pulses to be delivered andthe responses to be measured. From the measured responses, the externalprogrammer may determine the optimal electrode configuration, byselecting the electrodes to have an optimal response to a bipolar ormultipolar delivery of stimulation.

FIG. 2 illustrates a diaphragm electrode assembly 40 in accordance withthe invention for placement on the diaphragm 18 for sensing and/orstimulation of the diaphragm and/or phrenic nerve endings located in thediaphragm 18. The assembly 40 comprises a right loop 41 and a left loop42, each loop comprising a plurality of electrodes 41 a-h and 42 a-h,each having individual connectors and leads that form leads 43, 44coupled to the control unit 100. The loops 41, 42 are similar toelectrode assembles 41, 42 in that the electrodes are selectable by thecontrol unit 100 to form electrode pairs, multiple electrode pairs, ormultipolar electrode groups. FIG. 2 illustrates right phrenic nerveendings 15 a and left phrenic nerve endings 16 a as well as the rightphrenic nerve anterior branch 15 b, and left phrenic nerve anteriorbranch 16 b, located on the diaphragm abdominal surface 18 s. The loops41, 42 are flexible and are placed on the abdominal surface 18 s of thediaphragm 18 on the right diaphragm 18 r and left diaphragm 18 l,respectively adjacent the right phrenic nerve endings 15 a and leftphrenic nerve endings 16 a respectively. The flexibility of the loops41, 42 permits the ability to form the loops is the shape most ideallysuite for a particular patient. The loops 41, 42 are attached to thediaphragm 18 with sutures, staples or other attachment devices 19. Othershapes may be used as well, e.g. a loop with a branch that extends tothe region adjacent the anterior branches 15 b, 16 b of the phrenicnerve. The control unit 100 may be programmed to activate the electrodesin a sequence that is determined to elicit the desired response from thediaphragm 18 as described above with reference to electrodes 21 a-d, 22a-d and FIG. 1.

Referring to FIG. 3, a breathing disorder treatment apparatus 60according to the invention is illustrated. The apparatus 60 comprisesright and left electrode assemblies 61, 62 each comprising a pluralityof electrodes 61 a-61 d and 62 a-62 d respectively. The electrodesassemblies 61, 62 are illustrated attached to the right and left phrenicnerves 15, 16, respectively at a location in the neck 17. The electrodeassembly may be a curved cuff electrode that can be placed around thenerve. Procedures for accessing and attaching such electrode assembliesare generally know, for example, as described in Phrenic NerveStimulation For Diaphragm Pacing With a Spiral Cord Stimulator, Sur.Neurol 2003:59: 128-32.

FIG. 4 illustrates the device 60 of to FIG. 3 with electrode assemblies61, 62 alternatively positioned within the thorax 19 on the phrenicnerves 15, 16. The electrode assemblies 61, 62 are placedthoracoscopically on the phrenic nerve using a procedure similar to thatdescribed in Thoracoscopic Placement of Phrenic Nerve Electrodes forDiaphragmatic Pacing in Children; Journal of Pediatric Surgery, Vol. 37,into 7 (July), 2002: pp 974-978. The electrode assemblies 61, 62 arelocated between the third and fourth rib within the thorax 19. Thestimulator 60 is used in a similar manner in this FIG. 4 as it is withreference to FIG. 3.

FIG. 5 illustrates a stimulator 70 in accordance with the invention. Thestimulator comprises stimulating electrode assemblies 71, 72 implantedin the diaphragm in a manner similar to that described above withreference to electrode assemblies 71, 72 in FIG. 1. The electrodeassemblies 71, 72 include electrodes 71 a-d, 72 a-d, configured todeliver stimulating pulses to the diaphragm and or phrenic nervebranches or junctions with the diaphragm to elicit a breathing responseby causing the diaphragm to move. The stimulator 70 further compriseselectrode sensor assemblies 75, 76 placed on the phrenic nerve at thethroat in a surgical procedure similar to that described above withreference to FIG. 1 and electrode assemblies 71, 72. The sensorassemblies 75, 76 comprise a plurality of electrodes that are positionedand configured to sense electrical activity of the phrenic nerve todetermine central respiratory effort. In response to sensed respiratoryeffort, the control unit 100 supplies EMG and/or nerve stimulation tothe muscles of the diaphragm 18 and/or the phrenic nerve endings 15, 16located in the diaphragm 18.

FIG. 6 illustrates an implantable control unit 100. The control unit 100includes electronic circuitry capable of generating and/or deliveringelectrical stimulation pulses to the electrodes of electrode assemblies21, 22, 41, 42, 61, 62, 71, 72 through leads 23, 24, 43, 44, 63, 64, 73,74 respectively to cause a diaphragm respiratory response in thepatient. For purposes of illustration, in FIG. 6, the control unit 100is illustrated coupled to through leads 23, 24 to electrode assemblies21, 22 respectively. Other leads 41, 42, 61, 62, 71, 72 as describedherein may be connected to inputs 101, 102.

The control unit 100 comprises a processor 105 for controlling theoperations of the control unit 100. The processor 105 and otherelectrical components of the control unit are coordinated by an internalclock 110 and a power source 111 such as, for example a battery sourceor an inductive coupling component configured to receive power from aninductively coupled external power source. The processor 105 is coupledto a telemetry circuit 106 that includes a telemetry coil 107, areceiver circuit 108 for receiving and processing a telemetry signalthat is converted to a digital signal and communicated to the processor105, and a transmitter circuit 109 for processing and delivering asignal from the processor 105 to the telemetry coil 107. The telemetrycoil 107 is an RF coil or alternatively may be a magnetic coil. Thetelemetry circuit 106 is configured to receive externally transmittedsignals, e.g., containing programming or other instructions orinformation, programmed stimulation rates and pulse widths, electrodeconfigurations, and other device performance details. The telemetrycircuit is also configured to transmit telemetry signals that maycontain, e.g., modulated sensed and/or accumulated data such as sensedEMG activity, sensed nerve activity, sensed responses to stimulation,sensed position information, sensed movement information and episodecounts or recordings.

The leads 23, 24 are coupled to inputs 101, 102 respectively, of thecontrol unit 100, with each lead 23, 24 comprising a plurality ofelectrical conductors each corresponding to one of the electrodes orsensors (e.g., strain gauge) of the electrode assemblies 23, 24. Thusthe inputs 101, 102 comprise a plurality of inputs, each inputcorresponding to one of the electrodes or sensors. The signals sensed bythe electrode assemblies 21, 22 are input into the control unit 100through the inputs 101, 102. Each of the inputs are coupled to aseparate input of a signal processing circuit 116 (schematicallyillustrated in FIG. 6 as one input) where the signals are thenamplified, filtered, and further processed, and where processed data isconverted into a digital signal and input into the processor 105. Eachsignal from each input is separately processed in the signal processingcircuit 116.

The EMG/Phrenic nerve sensing has a dual channel sensor. Onecorresponding to each lung/diaphragm side. However, sensing can beaccomplished using a single channel as the brain sends signals to theright and left diaphragm simultaneously. Alternatively, the EMG orphrenic nerve collective may be sensed using a single channel. Either adual channel or single channel setting may be used and programmed. Thetypical pulse width parameter will range from 0.5 ms to 10 ms inincrements of 50 μs. The pulse amplitude is from about 0.1 v to 5 voltsin increments of 100 μV. The refractory period is 1 to 10 seconds inincrements of 1 second. As described in more detail with reference toFIGS. 10A-10B herein the system may adjust the pace, pulse, frequencyand amplitude to induce or control rate of the various portions of arespiratory cycle, e.g. slope of inspiration, fast exhalation,exhalation and tidal volume. The system may also adjust the rate of therespiratory cycle.

The system EMG memory is programmable to pre-trigger and post triggerlengths of storage for sleep apnea episodes. The pre-trigger events arethe waveform signals and other sensed information observed transitioningto an event. Post-trigger events are the waveforms and other sensedinformation observed after an event and/or after treatment of an event,to observe how the device operated. Post-trigger recordings can confirmif the episode was successfully treated. The pre-trigger andpost-trigger time periods can be preprogrammed into the control unit100.

The control unit 100 includes a position sensor 121 configured to sensea relative position of the patient, e.g. angular position, and provide adigital signal corresponding to the sensed position to the processor105.

The control unit 100 also includes an accelerometer 122 configured tosense acceleration and movement of the patient and to provide a digitalsignal corresponding to the sensed movement to the processor 105. Inaddition, an accelerometer 122 is positioned within the control unit100. The accelerometer 122 measures the activity levels of the patientand provides the signal to the processor 105 for use in furtheranalysis. Using an accelerometer in the implanted device indicates theactivity level of the patient in conjunction with breathing rate. Theaccelerometer senses activity threshold as at rest, low medium or highdepending on the programmed threshold value for a specific patient.Using the activity (accelerometer) sensor value and respiratoryinformation, the health of the respiratory system may be evaluated andmonitored. For example, if a patient's respiratory rate increases withan increase in activity and decreases with a decrease in activity,within a normal range, the patient's system will be consideredfunctioning normally. If the patient's respiratory rate is out of rangeor too high while the activity sensor indicates at rest or low, then thepatient may be suffering from pulmonary edema. Using this monitor, theeffect of drug titrations, e.g., diuretic dosages, on a patient withpulmonary edema can be monitored. If the pulmonary edema patient'srespiration is brought more towards a normal range with a drug dose,then the drug treatment would be maintained. If the drug treatment didnot effect breathing sufficiently then the drug dosage may be increased.Accordingly, the drug dosage may vary with detected breathingirregularities.

A position sensor 121 is also located within the control unit 100 andhas an output coupled to the processor 105. The position sensor sensesthe relative angle of the patients' position. The position sensor isused to detect a patient's relative position, e.g., horizontal, supine,or standing. An available position sensor is the Spectrol 601-1045 smartposition sensor, self-contained device that provides an analog outputover a full range of 360 degrees without requiring external components.

The control unit 100 further includes a ROM memory 116 coupled to theprocessor 105 by way of a data bus. The ROM memory 118 provides programinstructions to the control unit 100 that direct the operation of thestimulator 40.

The control unit 100 further comprises a first RAM memory 119 coupledvia a data bus to the processor 105. The first RAM memory 119 may beprogrammed to provide certain stimulation parameters such as pulse orburst morphology; frequency, pulse width, pulse amplitude, duration anda threshold or trigger to determine when to stimulate. A second RAMmemory 120 (event memory) is provided to store sensed data sensed, e.g.,by the electrodes 21 a-d 22 a-d, 41 a-h 42 a-h, 61 a-d 62 a-d, 71 a-d,72 a-d (EMG or nerve activity), position sensor 121, diaphragm movementsensors or strain gauges 25, 26, or the accelerometer 122. These signalsmay be processed and used by the control unit 100 as programmed todetermine if and when to stimulate or provide other feedback to thepatient or clinician. Also stored in RAM memory 120 may be the sensedwaveforms for a given interval, and a count of the number of events orepisodes over a given time as counted bat the processor 105. Thesystem's memory will be programmable to store: number of sleep apneaepisodes per night; pacing stimulation and length of time; the systemicauto-correction (i.e., how stimulus was adjusted, e.g., in amplitudefrequency phase or waveform, to reach a desired or intrinsic levelresponse); body resumption of breathing; the number of apnea episodeswith specific durations and averages and trending information;hyperventilation episodes during supine position; number ofhyperventilation episodes during sleep position; number ofhyperventilation episodes during vertical position; and patientinformation including the medications and dosages and dates of changes.These signals and information may also be compiled in the memory anddownloaded telemetrically to an external device 140 when prompted by theexternal device 140.

An example of the circuits of the signal processing circuit 116corresponding to one of the EMG inputs for one of the electrodes orpairs of electrodes of the assemblies 21, 22 is illustratedschematically in FIG. 7A. An EMG signal is input into an amplifier 130that amplifies the signal. The signal is then filtered to remove noiseby filter 131. The amplified signal is rectified by a rectifier 132, isconverted by an A/D converter 133 and then is integrated by integrator134 to result in an integrated signal from which respiratory informationcan be ascertained. The signal output of the integrator 134 is thencoupled to the processor 105 and provides a digital signal correspondingto the integrated waveform to the processor 105. The signal output ofthe integrator 134 is also coupled to a peak detector 135 thatdetermines when the inspiration period of a respiratory cycle has endedand an expiration cycle has begun. The signal output of the integrator134 is further coupled to a plurality of comparators 136, 137, 138, 139.The first comparator 136 determines when respiration (EMG signal orphrenic nerve signal) has been detected based on when an integratedsignal waveform amplitude has been detected that is greater than apercentage value of the peak of an intrinsic respiratory cycle oranother predetermined amount (comp 1), for example between 1-25% of theintrinsic signal. In this example, the comparator is set at a value thatis 10% of the waveform of an intrinsic respiratory cycle. The secondcomparator 137 determines a value of the waveform amplitude (comp 2)when an integrated signal waveform amplitude has been detected that isat a predetermined percentage value of the peak of an intrinsicrespiratory cycle or another predetermined amount, for example between75-100% of the intrinsic signal. In this example, the comparator is setat a value that is 90% of the waveform of an intrinsic respiratorycycle. From this value and the comp 1 value, the slope of theinspiration period (between 10% and 90% in this example) may bedetermined. This slope may provide valuable diagnostic information as itshows how quickly a patient inhales. After (or when) the peak detectordetects the end of an inhalation period and the beginning of anexhalation period, the third comparator 138 determines an upper valuefor the waveform amplitude during active exhalation period, for examplebetween 100% and 75% of the peak value detected by the peak detector135. Then a lower value (comp 4) of the waveform during the exhalationperiod is determined by the fourth comparator 139, which compares themeasured amplitude to a predetermined value, e.g. a percentage value ofthe peak amplitude. In this example the value is selected to be 10% ofthe peak value. In one embodiment this value is selected to roughlycoincide with the end of a fast exhalation period. From comp 3 and comp4 values, the slope of the exhalation period (between 10% and 90% inthis example) may be determined. This slope may provide valuablediagnostic information as it shows how quickly a patient exhales.

FIG. 7B illustrates two sequential integrated waveforms of exemplaryintegrated signals corresponding to two serial respiratory cycles,described in more detail herein with reference to FIGS. 9A-9D. Thewaveform 170 has a baseline 170 b, inspiration cycle 171, a measuredinspiration cycle 172, a point of 10% of peak inspiration 173 (comp 1),a point of 90% of peak of inspiration 174 (comp 2), a peak 175 whereinspiration ends and exhalation begins, and exhalation cycle 176 a fastexhalation portion 177 of the exhalation cycle 176, a 90% of peakexhalation point 178 (comp 3), a 10% of peak exhalation point 179 (comp4), an actual respiratory cycle 160 and a measured respiratory cycle181. The second waveform 182 is similarly shaped. The 10% inspiration183 of the second waveform 182 marks the end of the measured respiratorycycle 181, while the 10% point 173 of the waveform 170 marks thebeginning of the measured respiratory cycle 181.

The system may adjust the pace, pulse, frequency and amplitude to induceslow and elongated inspiration period; and fast and short inspirationperiod. The system may match the intrinsic sleep or awake time tidalvolume by adjusting the output energy while sensing the EMG or nerveamplitude. This may be done gradually by frequently sensing andincrementally adjusting. The system may deliver elongated inspirationperiod while shortening the expiration period to control and manipulatethe PO₂ and PCO₂ levels in the blood to overcome and treat apnea. Thesystem may deliver time and amplitude modulation output for control ofinspiration and exhalation periods. To increase the inspiration period,the system may deliver fewer bursts at lower amplitudes and higherfrequencies. To create a fast, short inspiration cycle, the system maydeliver more of bursts at higher amplitudes. The system may deliversequential low energy pacing output either from one or multipleelectrodes to control and manage the pulmonary stretch receptorthreshold levels to avoid or prevent the collapse of the upper airways.FIG. 10 illustrates a variety of exemplary stimulation bursts andresulting effective EMG that may be used to control the various phasesof the respiratory cycle, including, e.g., slope of inspiration, fastexhalation, exhalation, tidal volume, peak value, and rate ofrespiration.

Referring to FIGS. 10A-10B, a first intrinsic EMG waveform 550 isillustrated in FIG. 10A. A subsequent EMG waveform 551 (FIG. 10A) isillustrated in response to a burst of pulses 561 (FIG. 10B) of symmetricamplitude, frequency and pulse width. A subsequent EMG waveform 552 isillustrated (FIG. 10A) in response to burst of pulses 562 (FIG. 10B).The resulting EMG waveform 552 (FIG. 10A) has a flatter inspirationslope and expiration slope and relatively lower peak amplitude. Thisparticular effect may be desirable to control breathing and create aslower more gradual inspiration. The burst 562 (FIG. 10B) comprises aseries of pulses increasing in amplitude and of a higher frequency thanburst 561 (greater number of pulses). The subsequent EMG waveform 551(FIG. 10A) has a relatively sharp inspiration slope. The correspondingburst 563 of pulses has fewer pulses (3) and higher amplitude pulses.The effect of this burst 563 is to increase inspiration rate. Thesubsequent EMG waveform 554 (FIG. 10A) has a relatively slow inspirationcycle as a result of a burst 564 (FIG. 10B) with both increasingamplitudes and longer pulse widths (and a greater pulse duration). Theseare a few examples of a multitude of possible variations of burst pulsesthat can be modified to control the inspiration, expiration, tidalvolume (area under waveform curve) and other parameters of therespiratory cycle by modifying frequency, amplitude, pulse width of thepulses within the burst and the duration of the burst to get a desiredeffect. These bursts can be modified and programmed into a stimulatorand may vary from patient to patient.

In FIG. 8 a circuit for an external device 140 is illustrated. Theexternal device 140 comprises a processor 145 for controlling theoperations of the external device. The processor 145 and otherelectrical components of the external device 140 are coordinated by aninternal clock 150 and a power source 151. The processor 145 is coupledto a telemetry circuit 146 that includes a telemetry coil 147, areceiver circuit 148 for receiving and processing a telemetry signalthat is converted to a digital signal and communicated to the processor145, and a transmitter circuit 149 for processing and delivering asignal from the processor 145 to the telemetry coil 146. The telemetrycoil 147 is an RF coil or alternatively may be a magnetic coil dependingon what type of coil the telemetry coil 107 of the implanted controlunit 100 is. The telemetry circuit 146 is configured to transmit signalsto the implanted control unit 100 containing, e.g., programming or otherinstructions or information, programmed stimulation rates and pulsewidths, electrode configurations, and other device performance details.The telemetry circuit 146 is also configured to receive telemetrysignals from the control unit 100 that may contain, e.g., sensed and/oraccumulated data such as sensed EMG activity, sensed nerve activity,sensed responses to stimulation, sensed position information, or sensedmovement information. Other information such as frequency and time ofapnea, number of apnea events detected in a time interval or during asleep cycle, parameter relating to pulmonary edema such as frequency ofhyperventilation including time and patient position. This informationmay be stored in RAM event memory 158 or may be uploaded and through anexternal port 153 to a computer, or processor, either directly orthrough a phone line or other communication device that may be coupledto the processor 145 through the external port 153. The external device140 also includes ROM memory 157 for storing and providing operatinginstructions to the external device 140 and processor 145. The externaldevice also includes RAM event memory 158 for storing uploaded eventinformation such as sensed information and data from the control unit,and RAM program memory 159 for system operations and future upgrades.The external device also includes a buffer 154 coupled to or that can becoupled through a port to a user-operated device 155 such as a keypadinput or other operation devices. Finally, the external device 140includes a display device 156 (or a port where such device can beconnected), e.g., for display visual, audible or tactile information,alarms or pages.

The external device 140 may take or operate in, one of several forms,e.g. for patient use, compliance or monitoring; and for health careprovider use, monitoring, diagnostic or treatment modification purposes.The information may be downloaded and analyzed by a patient home unitdevice such as a wearable unit like a pager, wristwatch palm sizedcomputer. The downloaded information may present lifestyle modification,or compliance feedback. It may also alert the patient when the healthcare provider should be contacted, for example if there ismalfunctioning of the device or worsening of the patient's condition.The system may prompt the patients with voice, music or other audiblealarms regarding compliance with medication, diet and exercise.Medication compliance is a major issue with heart failure patients dueto the difficulties created for the patients by some medications. Thepatient hand held also provides daily update regarding the status of thedevice and as well as whether patients need to see the physician and/orconsuming more or less of a medication according to the programmedparameters by the physician inside the implantable device. The devicemay also manage a patient's diuretic level in relationship to breathingfrequency and character. The device may monitor the response of thetreatment from measured parameters provided by the control unit 100 inresponse to diuretic usage that e.g., may be input by the patient. Thissystem may also warn the patient to check into a hospital based onphysician command (programming). The system could also direct thepatient to rest in different positions to alleviate the present problemuntil help arrives.

Another device that interfaces with the patient's home unit may also beused to provide information to the clinicians. Such device maycommunicate, for example via an internet, phone or other communicationdevice. It may download information from the patient and/or uploadinformation form the physician. It may provide physicians withinformation identifying when intervention may be necessary or to furtherdiagnose a patient's condition.

The external device may be equipped with a palm pilot type device thatconnects to the phone line for downloading the patient specificinformation regarding patient's pulmonary status as well as ofconditions including apnea, hypoventilation and hyperventilation, andwhether the parameters are programmed correctly. This device may allowfor remote follow-up, continuous monitoring of the patient's hemodynamicstatus, effectiveness of the drug regime and in particular themanagement of diuretics where the apnea is influenced by pulmonaryedema. The information may be viewed by the clinician using a webbrowser anywhere in the world of the handheld can send a fax or noticeto the physician's office once the parameters of interest are outsidethe programmed range. The physician may then request an office visit.The system also can send a summarized report on weekly, biweekly, ormonthly as routine update based on the decision of the physicianprogrammed in the handheld device. Medication adjustment/drug titrationmay be accomplished remotely. Hand-held communicationprotocol/technology may be magnetic or RF.

FIGS. 9A-9D illustrate the operation of a stimulator in accordance withthe invention. The EMG monitoring is turned on or started 200.(Alternatively, or additionally, the phrenic nerve activity may bemonitored in the sequences described in FIGS. 9A-9D). As illustrated inFIG. 9A-9B, the system is turned on and begins sensing respiratoryeffort. It determines the intrinsic rates of breathing cycles includingrespiratory period, inhalation period and exhalation period, and storesthe values in event memory (step 200). This may be done, e.g., bysensing when a patient is in a reclining position for a predeterminedperiod of time while their breathing normalizes to that near thebreathing rate when sleeping. A threshold level is then calculated fromthe intrinsic rate at some level below the peak of the intrinsicrespiratory effort level.

The presence of an EMG is detected 200 by detecting when the amplitudeof the integrated waveform 170 reaches a predetermined level, e.g., at apercentage of the total amplitude, or the intrinsic waveform of thebreathing rate when sleeping.

If there is no EMG detected 201 then the stimulator determines whethersleep apnea is present or not 300 by determining a lack of EMG orphrenic nerve activity in a given period of time, e.g., 5-10 seconds, orby an attenuated EMG, e.g., not reaching comp 1 or, e.g., not reachingcomp 2 in the case of partial apnea. If sleep apnea is present, then thestimulator goes to the apnea treatment module 301 or to a program wherethe apnea is treated (See FIG. 9B). If sleep apnea is not detected, thenthe stimulator determines if hypoventilation is present 400 bydetermining that the EMG is present at an intrinsic amplitude orpercentage thereof, but the rate is lower than the intrinsic rate. Ifhypoventilation is present then the stimulator goes to thehypoventilation treatment module 401 or to a program wherehypoventilation is treated. (See FIG. 9C.) If an EMG, apnea, andhypoventilation are not detected, then presumably the patient is notbreathing or there is a malfunctioning of the stimulator. If this is thecase, the system may be programmed to do an emergency of the componentsand then communicate to the patient or health care provider that thestimulator is malfunctioning and/or the patient is not breathing 250.This communication may be accomplished a number of ways via a variety ofongoing or periodic communication processes. The system may continue tolisten for an EMG 201 after the system does and emergency check (step250). After a given time or number of iterations of reaching step 250,the stimulator may sound an alarm.

If an EMG is detected at step 201, then the stimulator starts arespiratory timer 202 and the time and amplitude values are stored. Therespiratory timer will determine the amount of time in one givenbreathing cycle between the detected beginning of inspiration,exhalation and the detected beginning of the inspiration of the nextcycle. The inspiration timer will also be started 203. The inspirationtimer will time the duration of inspiration when detected, as describedwith respect to step 201, until the peak of the inspiration or thebeginning of expiration.

The slope of the inspiration cycle is determined 204 by determining theamplitude and time of that amplitude at a further point in time in theinspiration cycle (comp 2) from this information and the time andamplitude at the detection of the EMG (201).

A peak detector monitors the integrated waveform and determines when ithas peaked 205, marking the end of inspiration and the beginning ofexpiration. When the peak is detected the time or duration of theinspiration cycle is stored along with the amplitude 206. Theinspiration timer is then turned off 207 and the exhalation timer isstarted 208. In step 209 the values comp3 and comp 4 are determined as apredetermined percentage to the peak value. In step 210, a comparatorwill then compare the amplitude of the signal during exhalation to apredetermined value or percentage of the total amplitude as measured atthe peak until that value is reached. This predetermined value isreferred to herein as comp 3. The time is stored. In step 211, acomparator will then compare the amplitude of the signal duringexhalation to a predetermined lower end value or percentage of the totalamplitude as measured at the peak until that value is reached. Thispredetermined value is referred to herein as comp 4. The stimulator thendetermines the slope of the exhalation cycle based on time and amplitudevalues of comp 3 and comp 4. The value for comp 4 may be selected toapproximately mark the end of the fast exhalation period of theexhalation cycle, which is the initial period where the exhalation issharper. At this point, the exhalation timer is stopped and theamplitude value and time is stored 212. In step 213, the stimulator maythen determine the inhalation period, the exhalation period and theslope or curve characteristics of the breathing cycle during this timethe slope of the waveform during either exhalation and/or inspirationmay be recorded and analyzed to identify breathing irregularities. Theinhalation period and exhalation period may be respectively based on thetime values between the beginning of inhalation (comp 1) and the peak,and the peak (for inspiration) and the beginning of the peak and the endof the fast exhalation period. Also, the inspiration and expirationperiods may also respectively include a calculation or approximation ofthe time between the actual beginning of inspiration to the detectedbeginning of inspiration and a calculation of the time between the endof the fast exhalation (comp 4) and the end of the exhalation period.The slopes of each of the inspiration periods and expiration periods maybe calculated as well as the determination of other waveformcharacteristics that may provide useful diagnostic information. Afterthe end of the fast exhalation period has been determined the stimulatorthen determines the total respirator period. After a first inhalationand exhalation cycle of a first breath, the stimulator awaits to detecta second cycle. The stimulator waits to detect the presence of a comp 1value of an EMG 215. If the EMG is present then the time is stored, therespiratory timer is stopped, and the respiratory period is stored 216.The respiratory period may be a measured time from the detection of anEMG of a first waveform to the detection of an EMG of a second waveform.Alternatively, the respiratory period may be determined by adding theinitial undetected period of the first waveform and subtracting theinitial undetected period of the second waveform. The stimulator thendetermines if there is hyperventilation 217 by determining if the rateis a certain value or amount above the intrinsic rate for the particularaware, sleep or other state of the patient. If hyperventilation isdetected, then the stimulator goes to the hyperventilation module 501where hyperventilation is treated. If no hyperventilation is detected,the stimulator returns to its original monitoring step 201 where itawaits the next EMG detection and repeats the cycle.

FIG. 9B, illustrates the sleep apnea module 301. When sleep apnea isdetected 300, a determination is made as to whether apnea is completeapnea 302. Complete apnea would be determined by a complete lack ineffective or detected EMG (or alternatively, phrenic nerve activity). Ifthe apnea is not sleep apnea then a determination is made as to whetherthe apnea is partial apnea 320 where the EMG signal is attenuated apredetermined amount. If the apnea is obstructive apnea, an cut of chaseEMG may be detected as well.

If complete sleep apnea is detected 302, then the pacing outputparameters stored in RAM 120 are loaded 303, e.g., into a register. Thepacing output is then delivered 304. After delivering the pacing outputto the phrenic nerve and/or diaphragm muscle, the EMG is observed 305,if the EMG is not approximately at the intrinsic sleep level, then theparameters are adjusted to bring the EMG more within the appropriaterange 306 and elicit a response closer to intrinsic breathing. Forexample, if the frequency or amplitude is too low, then the frequency oramplitude of the pacing is adjusted upwards. If the frequency oramplitude is too high, then the frequency or amplitude of the pacing isadjusted downward. If the EMG is approximately at the intrinsic sleeplevel 305, then the monitoring period is increased by one second 307(e.g., the monitoring period may start at about 10 seconds with amaximum at about 15 seconds). The EMG is then monitored again to see ifapnea is present 308. If it is then the pacing output is continued 304.If it is then, if the monitoring period is not at a defined maximum 309then the monitoring period is increased one second and the EMG isobserved again 308 and as long as the EMG is present 308, the stimulatorwill keep increasing the monitoring period by one second 307 until themaximum monitoring period is reached 309. When the monitoring perioddoes reach a maximum level, the apnea is confirmed as being treated 310by observing the EMG for a given period of time, e.g. for 3 consecutiveEMG's. The parameters of stimulation and information regarding theepisode are stored 311 in event RAM 119, and the system returns to EMGmonitoring (step 200 of FIG. 9A).

If complete sleep apnea is not detected 302 then the stimulatordetermines if partial apnea is present 320. If partial apnea is notpresent, the system returns to the emergency check 250 to see if thesystem is malfunctioning. If partial apnea is present, then the existingEMG parameters are determined 321 and the pacing parameters are adjustedbased on the existing EMG 322 and are loaded 323 and are delivered 324.The existing EMG parameters may be determined a number of ways. Thesystem may attempt to match the desired EMG with the pacing output byadding on to the existing EMG. One method may involve calculating thetidal volume based on the peak value of the existing EMG voltage output,pulse width, thus area under the respiration curve; calculating thepacing energy (amplitude and frequency) required to achieve the tidalvolume (of an intrinsic sleep EMG); and increasing the EMG or pacing anincreased calculated amount to achieve the desired tidal volume.

If after delivering the pacing output 324, the EMG is not at theintrinsic sleep level 325, then the parameters are adjusted to elicitthe intrinsic response 331 and the parameters are loaded 3232 anddelivered 324 again. If the EMG is at the intrinsic sleep level 325 thenthe monitoring period is increased by one second 326, and EMG observedagain to determine if the partial apnea has been treated 327. If theapnea has not been treated, then the stimulator returns to deliveringthe pacing output 324. If apnea has been treated and the monitoringperiod is not at the maximum 328 then the monitoring time is increasedby one second 326, and partial apnea is detected 327, etc. until themonitoring period has reached its maximum time 328 throughout whichapnea is determined to have been successfully treated after the maximumperiod is reached apnea treatment is confirmed 329 by observing the EMGa predetermined period of time afterwards, e.g., for three consecutiveEMG's. The parameters and information regarding the episode are thenstored 330. The system then returns to detecting the EMG (step 200 ofFIG. 9A)

FIG. 9C illustrates the hypoventilation module 401. Afterhypoventilation is detected 400 by comparing the breathing rate to aprogrammed low threshold breathing rate for a particular condition orstate (e.g., waking, resting or sleeping), a pacing output designed toelicit the intrinsic rate is loaded and is delivered to the phrenicnerve and/or diaphragm 403. The EMG is then sensed 404 and the EMG iscompared to the intrinsic EMG amplitude and waveform 405. The output ofthe amplitude, rate and pulse width are adjusted to match intrinsic EMGmorphology 406. The monitoring period is then increased by one second407. If the natural breathing rate has been restored for the maximummonitoring period, the stimulator returns to the step of detectingpresence of EMG (step 200, FIG. 9A). If it has not, then the EMG issensed again 404, compared to the intrinsic rate 405, adjusted ifnecessary 406, and the timer incremented again 407 until the naturalbreathing has been restored. 408.

FIG. 9D illustrates the hyperventilation module 501. If hyperventilationis present 500, then the level of hyperventilation is classified asClass I (low), Class II (medium) or Class III (high) based on the ratean frequency of hyperventilation. These particular rates andclassifications may vary from patient to patient and may be programmedin by the health care provider. The time date, respiratory rate,frequency or hyperventilation and activity sensor are senses and storedin event RAM 119. If class I is determined 504, the patient is informedvia the handheld or home monitoring device 505 and the patient isnotified to further comply with diuretic medications 506. If class II isdetected 507, then the patient is informed and additional medication isrecommended based on a prescription programmed into the hand held device508. The device then requests feedback by way of the hand held device,regarding compliance 509. The health care provider is notified of thestatus by way of the remote system, telephone connection or otherwise,and the sensed information concerning the patient's status is uploaded510. If class III is detected 511, then the patient is requested tovisit the physician immediately and also to consume addition medicationaccording to the physician's recommendation 512. The health careprovider is notified via the remote system 512. The system then returnsto detecting and EMG (step 200, FIG. 9A).

While the invention has been described with reference to particularembodiments, it will be understood to one skilled in the art thatvariations and modifications may be made in form and detail withoutdeparting from the spirit and scope of the invention.

1-99. (canceled)
 100. A device for controlling respiration of a patientcomprising: at least one electrode configured to be coupled to tissue ofa patient's body wherein the at least one electrode is configured todeliver electrical stimulation to the tissue to thereby manipulate adiaphragm respiratory response; a sensor element configured to senseinformation corresponding to the patient's respiration; a breathingrelated disorder detector element coupled to the sensor element andconfigured to detect information corresponding to a breathing relateddisorder; an intrinsic breathing detector element coupled to the sensorelement configured to detect intrinsic breathing prior to onset of abreathing related disorder and resumption of intrinsic breathing afterelectrical stimulation delivered to the tissue; and a responsive elementcoupled to the breathing related disorder detector element and theintrinsic breathing detector element, wherein the responsive element isconfigured to control electrical stimulation delivered to the tissuethrough the at least one electrode in response to breathing relateddisorder detector element detecting information corresponding to abreathing related disorder, and to modify electrical stimulation inresponse to the intrinsic breathing detector element detectingresumption of intrinsic breathing.
 101. The device for controllingrespiration of a patient of claim 100 wherein the breathing relateddisorder detector element is an apnea detector.
 102. The device forcontrolling respiration of a patient of claim 100 wherein the breathingrelated disorder detector element is a hyperventilation detector. 103.The device for controlling respiration of a patient of claim 100 whereinthe breathing related disorder detector element is a hyponea detector.104. The device for controlling respiration of a patient of claim 100further comprising a memory element coupled to the sensor element andconfigured to store information sensed by the sensor corresponding tointrinsic breathing of a patient.
 105. The device for controllingrespiration of a patient of claim 104 wherein the intrinsic breathingdetector element is configured to compare sensed informationcorresponding to respiration of a patient to information stored in thememory corresponding to intrinsic breathing of a patient, to determinewhen intrinsic breathing has resumed.
 106. The device for controllingrespiration of a patient of claim 105 wherein the responsive element isconfigured to cease electrical stimulation in response to the intrinsicbreathing detector element detecting resumption of intrinsic breathing107. A method of controlling the respiration of a patient comprising thesteps of: sensing information corresponding to intrinsic breathing ofthe patient; monitoring subsequent breathing of the patient to detectinformation corresponding to a breathing related disorder; determiningwhether to electrically stimulate the tissue to elicit a diaphragmresponse in the patient, by detecting the information corresponding to abreathing related disorder; electrically stimulating the tissue tocontrol diaphragm movement in response to detecting apnea; determiningresumption of the intrinsic breathing in a patient after electricallystimulating the tissue to elicit the diaphragm response; and modifyingelectrical stimulation after determining resumption of the intrinsicbreathing.
 108. The method of claim 107 wherein the step of modifyingelectrical stimulation comprises ceasing electrical stimulation afterdetermining resumption of the intrinsic breathing.
 109. The method ofclaim 107 wherein the step of determining whether to stimulate comprisesdetermining the presence of apnea.
 110. The method of claim 107 whereinthe step of determining whether to stimulate comprises determining thepresence of hyperventilation.
 111. The method of claim 107 wherein thestep of determining whether to stimulate comprises determining thepresence of hypopnea.